Local drug delivery vehicles have been in development for different applications. A particular interest of this application is local drug delivery with non-implant vehicles that can deliver a therapeutic agent, a biological agent, cell base therapy, an active agent or a substance of any kind to a desired anatomical target and release it in a relatively short engagement time of seconds to minutes, hours or in some cases days. Potential applications include treating tumors or cancer of any kind, internal or external bodily injury sites, areas of inflammations or infections, treatment of stenosis or restenosis, vulnerable plaque, ischemic or hemorrhagic stroke, promotion of wound healing and other conditions that can be treated using therapeutic or other known agents. Examples of drug delivery vehicles may be found, e.g., in U.S. Pat. No. 7,105,013; U.S. Pat. No. 5,306,250; U.S. Pat. No. 5,370,614; U.S. Pat. No. 5,324,261; U.S. Pat. No. 5,707,385; US Patent Appl. Publ. No. 2005/0101522; US Patent Appl. Publ. No. 2003/0064965; US Patent Appl. Publ. No. 2008/0118544; and US Patent Appl. Publ. No. 2008/0255510.
One particular application is drug delivery to body lumens using devices such as drug coated balloons (DEB). Drug coated balloons release drug to luminal walls through surface contact and diffusion. The drug is typically utilized to minimize inflammatory response during healing and improve long term patency of the lumen. In other cases therapeutic agents include substances for accelerated or enhanced healing and of the luminal wall after balloon angioplasty.
Those devices suffer from multiple limitations that hinder their effectiveness. One of the key issues is binding the drug to the balloon surface in a way that will allow the drug to release at the desired target. Typically the coatings involve additives or binders to allow the drug to bind to the surface. One example is contrast agents previously used as an additive to Paclitaxel in coated balloon application. Another example is polymeric additive such as hydrogels that react to water based environment. Dip coating, spray coating and other methods are used to attach combinations of binders or additives and drugs such as paclitaxel, Rapamycin or others to the polymeric surface of the balloon. Those formulations of drugs and additives add complexity to device and may affect the absorbency and thereby potency of the drug. In addition the device releases not just the drug but also the additive that may interfere with the healing process and affect the long term results of the treatment.
Another related limitation is that some of the drug coated on the balloon washes out during catheter delivery to the target location (literature reports include numbers of up to 80%). Delivery times vary significantly from less than 30 seconds to sometimes up to 10 minutes depending on the location of the target lesion and on the tortuosity of the anatomical pathway leading to the target. Therefore the amount of drug remaining on the coated balloon varies significantly, and the amount of drug released to the lesion cannot be controlled properly.
Attempts have been made to resolve this issue by developing new binders, adding erodible protective layers, using protective sheaths that may or may not include perforations and hiding the drug within the balloon folds. New binders and any new entity used in the circulatory system carry a risk of adverse biological effects and impaired release kinetic. Erodible protective layers further complicate the coating process and may impair the controlled release by shortening drug diffusion time (since the protective layer has to erode first) and adding another loosely controlled time variable to the drug/tissue contact time. Protective sheathes of any kind cover the drug layer, limit diffusion time and typically require the drug to be mixed with other additive that can flow through the perforated sheath. All those methods shorten the drug diffusion time, limit the ability to control the release kinetic and by that hinder the safety and effectiveness of the therapy.
Another limitation of these devices is in cases of therapeutic substances that are very active and need to be isolated until they reach the target site—such as biological sealants and fibrin sealants that may start oxidation or curing processes immediately upon contact with body fluid. Therefore these substances should be isolated throughout the delivery, regardless of length or tortousity, until the moment they reach the target site where they are activated/released.
Another limitation of drug delivery vehicles such as coated balloons is the dependence on diffusion alone to release the drug to the target during very short contact times (typically in the order of seconds or minutes). Diffusion is highly dependent on the topology and pathology of the lesion. For example, if the lesion is calcified the calcium may act as a barrier to drug diffusion and not enough substance will diffuse to the lesion.
For all those reasons there is still a need to invent and develop new vehicles for drug delivery to luminal walls and other locations in the body that will maximize the drug/tissue interaction time, minimize the need for new formulations and additives, and allow for a controlled and effective release of drug and other substances to target locations.